title: Changes of the GPR17 receptor, a new target for neurorepair, in neurons and glial cells in patients with traumatic brain injury.
abstract: Unveiling the mechanisms participating in the damage and repair of traumatic brain injury (TBI) is fundamental to develop new therapies. The P2Y-like GPR17 receptor has recently emerged as a sensor of damage and a key actor in lesion remodeling/repair in the rodent brain, but its role in humans is totally unknown. Here, we characterized GPR17 expression in brain specimens from seven intensive care unit TBI patients undergoing neurosurgery for contusion removal and from 28 autoptic TBI cases (and 10 control subjects of matched age and gender) of two university hospitals. In both neurosurgery and autoptic samples, GPR17 expression was strong inside the contused core and progressively declined distally according to a spatio-temporal gradient. Inside and around the core, GPR17 labeled dying neurons, reactive astrocytes, and activated microglia/macrophages. In peri-contused parenchyma, GPR17 decorated oligodendrocyte precursor cells (OPCs) some of which had proliferated, indicating re-myelination attempts. In autoptic cases, GPR17 expression positively correlated with death for intracranial complications and negatively correlated with patients' post-traumatic survival. Data indicate lesion-specific sequential involvement of GPR17 in the (a) death of irreversibly damaged neurons, (b) activation of microglia/macrophages remodeling the lesion, and (c) activation/proliferation of multipotent parenchymal progenitors (both reactive astrocytes and OPCs) starting repair processes. Data validate GPR17 as a target for neurorepair and are particularly relevant to setting up new therapies for TBI patients.
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Franke
authors.forename: Chiara
authors.initials: C
authors.lastname: Parravicini
authors.forename: Davide
authors.initials: D
authors.lastname: Lecca
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.forename: Claudia
authors.initials: C
authors.lastname: Heine
authors.forename: Kristina
authors.initials: K
authors.lastname: Bremicker
authors.forename: Marta
authors.initials: M
authors.lastname: Fumagalli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rosa
authors.forename: Luca
authors.initials: L
authors.lastname: Longhi
authors.forename: Nino
authors.initials: N
authors.lastname: Stocchetti
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: De Simoni
authors.forename: Marco
authors.initials: M
authors.lastname: Weber
authors.forename: Maria P
authors.initials: MP
authors.lastname: Abbracchio
mesh_terms: D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D055815:Young Adult
chemical_list: C121670:GPR17 protein, human; D043562:Receptors, G-Protein-Coupled